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DIABETES MELLITUS (Clinical Features (Glycosuria, Microangiopathy, Fasting…

- - - - Oral contraceptive
      - Thiazide diuretics
    - - Severe hyperglycaemia causing dehydration w/o ketoacidosis
      - Occurs in elderly diabetics with adequate insulin to prevent ketoacidosis but inadequate to prevent gluconeogenesis
      - As a result, liver makes glucose which the increases serum osmolarity
      - Complication secondary to dehydration
        
        This leads to decreased tissue perfusion with lactic acidosis,renal shutdown & cerebral thrombosis
        
        Tx same as DKA
        
        Hyperviscosity
      - Thromboembolism increased due to hyperosmolarity therefore anticoagulants are needed.
  - - - Hyperglycaemia due to glycogenolysis & gluconeogenesis
      - Keto acidosis due to ketogenesis [ from excess acetly coA( beta oxidation) ] and lactic acidosis( anaerobic metabolism)
      - Sweet breath [ketogenesis produces acetoacetate which converts to acetone & ends in the blood, diffuses into lungs and is exhaled bcoz its volatile]
  - - - Contraceptives
      - Thiazide diuretics
      - Corticosteroids
    - - Surgical Resection
      - Haemochromatosis
      - Chronic Pancreatitis
    - - Acromegaly
      - Hyperthyroidism
      - Cushings Syndrome
- - - - Coronary Atheroma
        
        Leads to restriction of circulation
        
        Due to acc. of fats & scar tissue
        
        Degen. of bv artery walls
        
        Predisposing to Thrombi formation
      - Peripheral Vascular Disease
        
        BV outside heart & braiin narrow, block or spasms.
        
        (-) blood flow to peripheral tissues
        
        Gangrene of feet & toes
        
        Ischaemic & neuropathic ulceration
        
        superimposed infxn in deep tissues(Cellulitis) & bone (Osteomyelitis)
        
        Diabetic foot
      - Atherosclerosis
        
        Early onset bcoz DM accelerates it
        
        More severe for DM
      - Cerebrovascular Accident
        
        Stroke
        
        Rupture (hemorrhagic) OR obstruction (ischaemic) of BV
    - - OR
      - Direct effect of chronic hyperglycaemia causing peripheral neeuropathy
      - BM thickening with subsequent capillary closure resulting in ischaemic demyelination & axonal degeneration
    - - Thickening of basement membrane
        
        Kidney
        
        Thickening of BM
        
        With altered charge
        
        Leading to proteinuria
        
        And so (+) permeability
        
        Pyelonephritis
        
        Thickened vessel BM
        
        These lead to poor acute inflammatory response to bacteria
        
        (+) sugar in urine
        
        Kimmelstiel-WIlson lesions
        
        Nodules of (+) mesangial matrix (glomerulosclerosis)
        
        Granular capsule
        
        Cut Surface
        
        Hilar fat
        
        Pale cortex
        
        Renal Papillary Necrosis
        
        Vessel changes in papillae
        
        Leads to infarction of papillae
        
        Swelling from pyelonephritis
        
        Pregnancy
        
        Polyhydramnios
        
        Premature contractions & labor
        
        Early membrane rupture
        
        Neontal Distress Syndrome
        
        Thus bcoz of lack of surfactant
        
        Lungs immature
        
        Too much insulin in fetus delays surfactant production
        
        Large foetus
        
        This leads to obstructed labor
        
        The excess glucose is stored and deposited as fat causing the fetus to be Macrosomiac
        
        Responds by producing lots of insulin to ensure use of the glucose.
        
        In maternal hyerglycaemia, fetal pancreas senses high glucose
        
        Which can lead to birth injuries
        
        This induces islet cell hyperplasia
        
        Pregnancy Induced HPT
        
        (+) congenital malformations
        
        EYE
        
        Microaneurysms
        
        Haemorrhages
        
        Diabetic retinopathy
        
        Exudates
        
        All can lead to blindness
  - - - Hypoglycaemia
        
        From insulin overdose
      - Hyperglycaemia with:
        
        HONK
        
        Lactic Acidosis
        
        Ketoacidosis
  - - - (-) myoinositol
        
        (+) injury Schwann cells & pericytes
      - Water into cell
        
        Leads to damage
    - - (+) matrix & BM
      - Inflammation & cytokines
      - Angiogenesis
    - - Harmful compounds formed when protein covalently combine with sugar in bloodstream.[ glycation]
      - AGE binds to RAGE(receptor) expressed on inflamm. cells
        
        (+) synthesis of matrix
        
        Atheroma
        
        (+) growth factors from mesangium & macrophage
        
        Proinflammatory molecules and cytokines
      - Sheer stress ( all mentioned cause this)
        
        due to (-) elasticity of CT
        
        Basement membrane of blood vessel:
        
        (-) breakdown
        
        (+) protein deposition
        
        (+) fluid infiltration
        
        (+) LDL trapping
      - Hyperglycaemia accelerates process
      - The glucose alter the conformation of glycated proteins and therefore affects their function.